Efforts to control body weight through diet, exercise and drugs have met with only limited success. Obesity continues to be of epidemic proportions in the USA. It was estimated that in 2000, more than 64.5% of the US adult population were overweight or obese and across the US, 30.5% of the population were obese (Flegal et al., JAMA 288: 1723-1727 (2002)). There also appears to be a US epidemic in diabetes with 7.3% of the US population being diabetic (Mokdad et al., JAMA 286: 1195-1200 (2001)). While physicians advise their patients battling with weight gain, obesity and diabetes to exercise and manage the quantity as well as the quality of food eaten, the evidence suggests that a major portion of the population are unable or unwilling to make the major changes in lifestyle that may be necessary to decrease their body mass.
The strategies recommended by health care providers to reduce and/or maintain weight often involve changes in life style and in some cases the additional use of drugs or dietary supplements. Those individuals that are able to maintain weight loss (defined as >10% below the initial body weight after one year) generally adopt all or at least some combination of these strategies (McGuire et al., “Behavioral strategies of individual who have maintained long-term weight losses” Obes Res 7:334-341 (1999)). Nonetheless, despite all of the efforts made by obese individuals and governments, the success rate for keeping weight off is disappointingly low. A meta-analysis has shown that the success rate of “self-cure” ranged from 9% to 43% afler a one-year follow-up (Bartlett et al., “Is the prevalence of successful weight loss and maintenance higher in the general community than the research clinic?” Obes Res 7:407-413 (1999)). The National Weight Control Registry has reported that 47%-49% of the obese patients maintained at least 10% weight loss after one year and 25% -27% have maintained this amount of weight loss over 5 years (McGuire et al., “The prevalence of weight loss maintenance among American adults” Int J Obes Metab Disord 23:1314-1319 (1999)). However, after 5-15 years, only 5% of the obese patients were able to maintain the weight loss (Drenick and Johnson, “Weight reduction by fasting and semistarvation in morbid obesity: long term follow-up”. Int. J Obes. 2:25-34 (1978) and Sarlio-Lahteenkorva and Rissanen “A descriptive study of weight loss maintenance: 6 and 15 years follow-up of initially overweight adults” Int J Obes 24:116-125 (2000)).
Pharmaceutical treatments for obesity have been developed but their use has limitations. Currently there are only two Food and Drug Administration (FDA) approved antiobesity drugs, Orlistat and Sibutramine. Orlistat inhibits pancreatic lipase activity in the small intestine. Pancreatic lipase breaks down triglycerides into fatty acids and monoglycerides which are subsequently absorbed into the body. Thus inhibition of lipase activity effectively reduces fat absorption. However, if the patient fails to follow a reduced fat diet, which is recommended while on this medication, the fat is metabolized by the intestinal bacteria and causes osmotic shifts and gas production resulting in diarrhea and flatulence, rather unpleasant side effects of this medication. Thus, while this drug can induce modest weight loss and better weight maintenance than diet alone, in the absence of major dietary changes the adverse effects of gastrointestinal discomfort, diarrhea and flatulence have limited its use (Heck et al., “Orlistat, a new lipase inhibitor for the management of obesity”. Pharmacotherapy 20:270-279(2000)).
Sibutramine is a serotonin and norepinephrine reuptake inhibitor and reduces body weight by suppressing appetite (Bray G., “Drug treatment of obesity”. Rev Endocr Metab Disord 2:403-418(2001)). FDA has approved it for the treatment of obesity for up to 2 years. However, Sibutramine inhibits the reuptake of norepinephrine and thus may increase blood pressure. Therefore this drug is contraindicated for use in some obese patients (Bray 2001 supra and Sramek et al. “Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomized trial” J Hum Hypertens 16:13-19 (2002)). Other side effects of Sibutramine include increased heart rate, insomnia, constipation, headache, abdominal pain etc. For normotensive obese patients, Sibutramine in combination of diet and behavioral modifications has shown beneficial effects (Astrup and Toubro “When, for whom and how to use sibutramine?” Int J Obes Relat Metab Disord 25 (suppl 4):S2-S7 (2001)) but to date there have been no human studies that used Sibutramine alone, that is without any life-style modifications. In addition, in one animal study, the appetite suppressing effects of Sibutramine gradually attenuated over several days of administration (Strack et al. “Regulation of body weight and carcass composition by sibutramine in rats” Obes Res 10:173-181 (2002)).
Dietary supplements have also been used to reduce weight gain, to maintain weight and to treat some of the metabolic abnormalities associated with obesity. For example, omega 3-fatty acids and linolenic acid have been shown to reduce weight gain and affect triglyceride levels and/or insulin resistance. Omega 3 fatty acids are known to reduce blood lipid levels in normal, hyperlipidemic and diabetic humans and have been reported to decrease body weight. Diabetic patients without hyperlipidemia fed a diet comprising fish oil, which is known to be high in omega 3 fatty acid, did not display reduced blood lipid levels, although their blood pressures were reduced. However, diabetic patients having hyperlipidemia had significantly reduced blood triglyceride levels and reduced blood pressure after the omega 3 fatty acid fish oil feeding (Kasmin et al. J. Clin Endocrinol Metab 67:1-5 (1988)). The effect of diets comprising fish oil fed to genetically obese Zucker rats and their lean counterparts demonstrated that both the obese and normal rats had a reduction in body weight and blood lipid levels as compared to controls (Jen et al., Nutrition Research 9:1217-1228 (1989)). A high fat diet made with fish oil induced the least amount of weight gain and insulin resistance compared to a high fat diet made with other types of oil(Pellizzon et al., Obesity Res. 10:947-955 (2002)) Omega 3 fatty acids also appear to beneficially affect insulin resistance. Rats fed high fat diets comprising fish oil had less insulin resistance than rats fed diets comprising other oils, e.g., lard, corn oil or medium chain triglycerides (Hill et al. Int. J. Obesity, 17:223-236 (1993)).
Linolenic acid added to diets has also been shown to reduce body fat content and to facilitate fatty acid β-oxidation in the liver (Takada et al., J. Nutr. 124:469-474 (1994)). Aged rats were fed diets made with various fatty acids, i.e., α-linolenic acid (n-3 PUFA) or gamma linolenic acid (n-6 PUFA) (10% w/w) with added cholesterol for 15 weeks and it was found that both the α-and gamma linolenic diets inhibited the increase in blood total cholesterol, VLDL+IDL+LDL cholesterol levels in the rats when fed high cholesterol diets (Fukushima et al. Lipids 36:261-266 (2001)). Similar results were found in obese Zucker rats which had reduced body weight gain and body fat when gavaged daily with gamma linolenic acid (Phinney et al. Metabolism 42:1127-1140 (1993)). In humans, a mixture of n-3 PUFA and gamma linolenic acid also favorably altered blood lipids and fatty acid profiles in women after administration for about 28 days (Laidlaw and Holub, Am J. Clin. Nutr. 77:37-42 (2003)).
Life style changes to promote weight loss and other beneficial health effects include e.g. an increase in physical activity; a reduced caloric intake and a reduced dietary fat intake. The United States has seen a gradual reduction in the percentage of dietary fat intake from 43.7% in 1965 to 33.1% in 1995 (Kennedy et al., “Dietary-fat intake in the US populatio” J Am Coll Nutr 18:207-212 (1999)), however, the average number of calories eaten has increased more than the increase in fat consumption. Therefore even though the percentage of dietary fat intake has decreased, the total fat intake has increased since 1995 to 100.6 g (males). Due to the relative ease with which dietary fat is converted to adipose tissue, a diet high in fat leads to an elevated weight gain as compared to a lower fat diet even though the calorie intake is comparable. This phenomenon has been reported to occur in both humans and rats (Astrup et al., “Obesity as an adaptation to a high-fat diet: evidence from a cross-sectional study” Am J Clin Nutr; 59:350-355 (1994)); (Jen “Effects of diet composition on food intake and carcass composition in rats” Physiol Behav 42:551-556 (1988) and; Jen et al., “Long-term weight cycling reduces body weight and fat free mass, but not fat mass in female Wistar rats” Int J Obesity 19:699-708 (1995)).
Various low fat and/or low calorie foods have been developed in an effort to promote weight loss or inhibit weight gain. Many “low fat” foods are prepared by reducing the percentage of fat but the percentage of carbohydrates in the foods is increased to make the foods more palatable by compensating for the loss of the taste and texture provided by the fat. Increasing the amount of carbohydrates, e.g., sugars, in the food often make the foods “low fat” but the caloric content may not be reduced and in many instances is actually increased. Many low calorie food are prepared by simply replacing the caloric components of the food with a non-caloric filler, e.g., a dietary fiber. However, replacing significant portions of carbohydrates with fiber fillers often alters the taste and texture of the food making the food less palatable for some consumers. In addition, consumption of large amounts of dietary fiber often have unwanted side effects such as e.g., flatulence, and a diet comprising more than about 60 g fiber may result in deficiencies in calcium, iron, zinc and increased risk of bowel obstruction. While high fiber diets, comprising about 25-35 g/d are recognized as having beneficial effects, e.g., reducing blood triglycerides and cholesterol levels, many persons should not take high levels of fiber, e.g., the elderly, growing children and those suffering from particular medical conditions e.g., acute or subacute diverticulitis, and the acute phases of certain inflammatory conditions of the bowel, e.g., ulcerative colitis or Crohn's disease. After some types of intestinal surgery, e.g., a colostomy or ileostomy, a low fiber, low residue diet is used as a transition to a regular diet is preferred. Thus it is desirable to develop a food product that has the taste and texture desired by consumers but also reduces weight gain, blood triglycerides and cholesterol levels and is not necessarily high fiber.
Cyclodextrins are a family of cyclic polymers of glucose produced by enzymatic digestion of cornstarch with a cyclodextrin glyceryltransferase. α-, β- and γ-cyclodextrins contain 6, 7 and 8 glucose molecules and take on a toroid or truncated cone conformation in aqueous solution. The molecules have a hydrophobic interior and hydrophilic exterior forming an internal pore. The different polymer lengths yield different pore sizes.
The unique properties of β and γ-cyclodextrins have been exploited in a variety of fields. For example, they have been used to stabilize and solubilize drugs and also to enhance food flavors. While the β and γ-cyclodextrins have found considerable use in the pharmaceutical and food industries., α-cyclodextrin has found relatively little use in these industries because of its small pore size as well as the fact that it does not appear to be metabolized by pancreatic amylase or intestinal flora (Suzuki and Sato, “Nutritional significance of cyclodextrins: indigestibility and hypolipemic effect of α-cyclodextrin” J Nutr Sci Vitaminol (Tokyo) 1985; 31:209-223), although this latter aspect has been disputed by one of the manufacturers of the material (Antlsperger G S G. “Toxicological comparison of cyclodextrins” presented in the 8th International Cyclodextrin Symposium in Budapest 1996:1-7). α-cyclodextrin efficiently complexes free fatty acids (FFA) in solution (McGowan et al. “A peroxidase-coupled method for the colorimetric determination of serum triglycerides” Clin. Chem. 29(3):538-542 (1983)) and has been used to eliminate the turbidity caused by FFA in a number of clinical diagnostic reagents (Morgan, Artiss and Zak “A study of turbidity in hypertriglyceridemic specimens” Microchem. J. 64:147-154(2000)). α-cyclodextrin has also been used for the specific and selective removal of free fatty acids from used cooking oil (U.S. Pat. No. 5,560,950).
Previous studies disclose that α-cyclodextrin is essentially indigestible and may exert an effect on weight gain only if it exceeds about 20% of the total dietary intake, as determined in a rat model. Japanese patent application JP 05-298849 (Publ. No. 07115934) assays the effects of linolenic acid and α-cyclodextrin on weight gain in rats. This application reports that rats fed diets comprising either 16% α-cyclodextrin or 1% linolenic acid gain weight approximately the same as rats fed a control diet. In contrast, this Japanese application discloses that rats fed diets comprising a combination of 14% α-cyclodextrin and 2% linolenic acid incur significant weight loss. Japanese patent application S60-149752 also analyzes the effect of linolenic acid in combination with α-cyclodextrin on weight gain in rats. This application reports that a diet comprising 14% w/w α-cyclodextrin has little effect on weight gain in rats while the combination of 14% w/w α-cyclodextrin and 0.5% w/w linolenic acid produces significant weight loss. Japanese patent application H5-298850 analyzes the effects of diets comprising linolenic acid (1.5-2% w/w) and α-cyclodextrin (14% w/w) and a barley green element. This application reports that the diets comprising 14% w/w α-cyclodextrin in combination with 1.5-2% w/w linolenic acid produce only a small decrease in body weight while the addition of a barley green element to the linolenic acid and cyclodextrin results in significant reduction in weight gain. This application does not report the effects of diets comprising only α-cyclodextrin as the additional component. None of these applications discloses the fat content of the diets and they teach the importance of additional ingredients and/or the ineffectiveness of α-cyclodextrin alone.
Japanese patent application H4-333575 supplemented the diet of rats with particular total amounts of linolenic acid and/or α-cyclodextrin and/or a peptide hydolysate by gavaging rats with wheat starch compositions comprising either 0.9% w/w linolenic acid alone, 9% w/w α-cyclodextrin alone, or 100% w/w of a compositions of small molecular weight hydrolytes of a larger molecular weight protein, or with compositions comprising combinations of the three components. The fat content of the diets was not described. Only the diets containing a combination of linolenic acid, α-cyclodextrin and the peptide hydrolysate displayed a significant change in the rate of weight gain over time.
Japanese applications JP05-113603 (Publ. No. 08187060) and JP05-164024 (Publ. No. 06343419) assay the effect of a mixture of about 15% α-cyclodextrin and 1.5% linolenic acid on weight gain in humans. The applications disclose that subjects ingesting the α-cyclodextrin/linolenic acid compositions in an amount based on their body weight, such that the daily dose of the composition was about 0.015 g/kg body weight three times a day, which is 1.37 g/91 kg (2001b) individual three times per day, which corresponds to 4.11 g of total composition per day or 0.62 g α-cyclodextrin per day (0.21 g/meal) and 0.068 g linolenic acid per day (0.023 g/meal), display a significant increase in weight loss as compared to subjects who did not ingest the combination. However, these applications did not assay the effect of α-cyclodextrin alone or linolenic acid alone nor did they disclose the fat content of the diets. Linolenic acid is well known to reduce weight and fat gain in both animal and human studies (Jen et al., Nutri. Res 9:1217-1228 (1989) and Takada et al., J. Nutri. 124:469-474 (1994) and Couet et al. Int. J. Obes. 21:637-643 (1997)) and is likely to be the component that actually promoted the observed weight loss reported in these applications.
U.S. Pat. No. 4,880,573 discloses a process for eliminating cholesterol from fatty substances of animal origin, e.g. lard, suet or butter. The process combines β-cyclodextrin with the liquified fatty substance under a non-oxidizing atmosphere and then removes the complexes of cholesterol and cyclodextrin leaving a fatty substance free of cyclodextrin and with a reduced cholesterol content.
U.S. Pat. No. 5,189,149 discloses the use of complexes of cyclodextrins and long chain fatty acids, their salts and esters, inclusive of fish and vegetable oil glycerides, to deliver long chain fatty acids to a subject and avoid the unctuous characteristics associated with the fish and vegetable oil glycerides and their unpleasant taste and odor.
U.S. Pat. No. 5,232,725 relates to a process for reducing the cholesterol and free fatty acids in a fat containing material, e.g., fresh cream, by combining water, the fat containing material and cyclodextrin under conditions suitable for forming an oil-in-water type “fine” emulsion, which facilitates the formation of complexes of cyclodextrin and cholesterol or free fatty acids. The complexes are then mechanically separated to produce a fat-containing material with reduced levels of cholesterol and free fatty acids. U.S. Pat. No. 5,232,725 does not describe a food product comprising complexes of triglyceride and α-cyclodextrin, wherein the bioavailability of the fat in the food product is reduced, as described herein.
U.S. Pat. No. 5,560,950 relates to a process for reducing the free fatty acid content of a used oil by mixing the used oil with cyclodextrin, preferably with an absorbent, e.g., silica, under conditions that form agglomerates of cyclodextrin/absorbent and fatty acids and then removing the cyclodextrin agglomerates from the oil. The process produces a oil that is cyclodextrin free and has a reduced level of free fatty acids.
U.S. Pat. No. 5,571,554 relates to a process for reducing triglycerides in an egg yolk by preparing a mixture of egg yolk with water, or a salt solution, and combining the mixture with a cyclodextrin and then removing the cyclodextrin and the added water or salt solution. The process produces a cyclodextrin free egg yolk product with reduced levels of triglycerides.
U.S. Pat. No. 5,738,898 relates to a process for reducing cholesterol in egg yolk by preparing a mixture of egg yolk, water and cyclodextrin at a pH between 7.5 and 12. The cyclodextrin cholesterol complexes are removed and the pH adjusted to pH 6-7. The process produces a cyclodextrin free egg yolk product with reduced cholesterol.
Many consumers, including obese individuals, appear to have a preference for foods that have a high fat content (Mela and Sacchetti, “Sensory preferences for fats: relationships with diet and body composition” Am J Clin Nutr 1991;53:908-915). Thus, it is very difficult for many individuals, particularly obese individuals, to reduce their fat intake in order to reduce their body weight and the adverse health effects associated with increased weight gain. Therefore, a substance that reduces the absorption of dietary fat without the unpleasant side effects of the current medications is extremely desirable. Such a substance would have significant health benefits in reducing obesity and its related disorders, such as Type II diabetes (NIDDM). It would be desireable to develop a food product that promotes weight loss, reduces lipid levels and reduces the symptoms of other disorders associated with weight gain/obesity and yet has desirable organoleptic properties. Described herein are fat containing consumable products having the organoleptic properties such as taste, texture and moistness that consumers desire and yet promote weight loss and other health benefits.